Additional studies will be undertaken to define the mechanism of action of thyroid hormone at a cellular level. Efforts will be directed to purify and characterize the nuclear T3 receptor. To this end we shall attempt to develop an affinity chromatography system for purifications. Prior to definitive purifications we shall assess the binding of T3 to solubilized nuclear receptor sites in the .4M KC1 extract at various temperatures. We shall attempt to determine with such data the thermodynamic properties of the binding reaction. Clinical studies will also be undertaken to measure potential changes in T3 and T4 nuclear occupancy in patients with nonthyroidal disease exhibiting low concentration of these hormones in plasma. Further studies will be undertaken to assess the nature of the T3-carbohydrate interaction at the nuclear level. These studies will be conducted both in the intact animal as well as in tissue culture preparations.